Recent evidence suggests that the progression of renal fibrosis is a reversible process, at least in experimental models. The present review summarizes the new insights concerning the mechanisms of progression and regression of renal disease and examines this novel evidence under the light of feasibility and transfer to human nephropathies. The involved mechanisms are discussed with particular emphasis on the fibrotic role of vasoactive peptides such as angiotensin II and endothelin and growth factors such as transforming growth factor (TGF)-beta. The possibility of regression is introduced by presenting the in vivo efficiency of antihypertensive treatments and of systems that antagonize the fibrogenic action of TGF-beta such as bone morphogenic protein-7 and HGF. Finally, we provide a brief description of the promising future directions and clinical considerations about the applications of the experimental data to humans.